See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on allelic variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Individuals meeting the strict diagnostic criteria of upper-limb defect and personal and/or family history of structural or conductive heart disease have a heterozygous TBX5 pathogenic variant predicted to cause disease [McDermott et al 2005, Debeer et al 2007]. Lower pathogenic variant detection rates (30%-40%) reported in some studies likely result from the inclusion of individuals who would not meet the strict diagnostic criteria outlined above [Cross et al 2000, Brassington et al 2003].

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

Deletion of one or more exons or the entire gene was detected in about 2% of individuals with HOS who did not have a pathogenic variant identified by sequence analysis/variant scanning [Borozdin et al 2006].

That current molecular analysis fails to identify a heterozygous pathogenic variant in TBX5 in up to 30% of individuals with HOS suggests the presence of pathogenic variants in noncoding regions or regulatory regions around TBX5 [McDermott et al 2005, Debeer et al 2007].